Different pharmaceutical formulation strategies have been used to enhance the bioavailability of drugs that are suffering from poor aqueous solubility. These include; size reduction by nano-sizing and micronization, use of cosolvents and surfactants, solid dispersion, and inclusion complexation. Moreover, formation of colloidal drug delivery systems such as solid lipid nanoparticles (NP), polymeric based NP, lipid based NP, microemulsion formation and self-microemulsifying drug delivery systems have attracted increasing attention. The solid dispersion technique, first introduced in the early 1970s, is the distribution of a hydrophobic drug(s) in and around a hydrophilic polymer(s) in the solid state. Melting (fusion), solvent evaporation, melt-extrusion and super critical anti-solvent processes are commonly used to prepare solid dispersions. Polyvinyl pyrrolidone (PVP) namely; poly-[1-(2-oxo-1-pyrrolidinyl)-ethylene], is a water-soluble polymer that has been utilized in solid dispersion preparations to improve solubility and dissolution of many water insoluble drugs.
Vinpocetine (VPN) is a derivative of the alkaloid vincamine which has been reported to have vasodilator, anti-ischemic, anti-convulsant, anti-inflammatory and neuroprotective activity. It is a weak basic drug (pKa=7.31) with a limited water solubility of 2.4 gig/mL. The main mechanism of drug action is attributed to inhibition of the enzyme phosphodiesterase (PDE) type-1 that results in increase in the level of 3,4-dihydroxyphenylacetic acid (DOPAC), a metabolic breakdown product of dopamine, which selectively enhances the brain circulation and oxygen utilization without significant modification in systemic circulation parameters. It facilitates blood flow redistribution towards ischemic areas, and enhances cerebral circulation and oxygen utilization. The major concerns about VPN are the poor aqueous solubility, short elimination half-life (1-2 h), and the extensive first pass metabolism (75% metabolism in liver) that limit the drug bioavailability. VPN is currently administered as an oral tablet containing 5 mg of the drug but with poor oral bioavailability. Several drug delivery systems have been employed in an attempt to overcome VPN delivery drawbacks, such as mixed polymeric micelles, solid lipid nanoparticles and self-microemulsifying drug delivery systems. However, none of these has been very successful and it would be highly beneficial to have available improved formulations that enhance the drug's aqueous solubility and bioavailability for the effective treatment of cerebral degenerative diseases.